Cigarette Smoking Affects Urinary Liver-Type Fatty Acid–Binding Protein Concentration in Patients With Early Diabetic Nephropathy

Cigarette smoking causes a decrease in the glomerular filtration rate in diabetic patients with normal renal function, independent of confounding factors including severe proteinuria (1). It increases the risk of microalbuminuria and accelerates the progression from microalbuminuria to overt proteinuria as well as the progression of renal failure in patients with type 2 diabetes (2). It is widely accepted that the rate of functional decline correlates with the degree of renal tubulointerstitial fibrosis. Previous studies have shown that renal function in patients with type 2 diabetes correlates better with tubular changes than with glomerular pathology (3). Further studies on tubulointerstitial injury in patients with diabetic nephropathy may provide additional insight into the pathogenesis of diabetic nephropathy and lead to the identification of therapeutic targets. Liver-type fatty acid–binding protein (l-FABP) is expressed in the proximal tubules, where it plays a key role in fatty acid metabolism. We and other investigators reported that urinary l-FABP may be a useful clinical marker for type 2 diabetic nephropathy (4–6). However, little is known about the effect of cigarette smoking on the urinary l-FABP level.

Fifty type 2 diabetic patients with microalbuminuria (28 men and 22 women, mean age 50.0 years), including 30 smokers (18 men and 12 women) and 20 nonsmokers (10 men and 10 women), were enrolled in the present study. No patient had a serum creatinine (Cr) level >1.2 mg/dl. Urinary l-FABP levels were measured by an enzyme-linked immunoassay kit as described previously (4–6). The urinary l-FABP level was significantly higher in smokers (20.5 ± 10.5 μg/g Cr) than in nonsmokers (10.5 ± 5.5 μg/g Cr) (P < 0.05). The smokers were divided into two groups: those who stopped smoking (n = 10, group A) and those who continued smoking (n = 20, group B). The angiotensin receptor blocker, ACE inhibitor, statin, antidiabetic drugs, and antiplatelet drugs used in the two groups were similar. After 24 months, the urinary l-FABP level in group A decreased significantly from 21.5 ± 10.0 to 13.5 ± 8.0 μg/g Cr (P < 0.05); however, that in group B increased significantly from 20.0 ± 11.0 to 27.5 ± 15.5 μg/g Cr (P < 0.05). These data suggest that cigarette smoking may be associated with tubulointerstitial injury in patients with early diabetic nephropathy.